UniProtKB/Swiss-Prot P14920: Variant p.Arg38His

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 38 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B The variants are classified into three categories: LP/P, LB/B and US.

• LP/P: likely pathogenic or pathogenic.
• LB/B: likely benign or benign.
• US: uncertain significance

Residue change: From Arginine (R) to Histidine (H) at position 38 (R38H, p.Arg38His). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: Change from large size and basic (R) to medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: 0 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

• Lowest score: -4 (low probability of substitution).
• Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description: Found in a patient with ALS; impairs FAD binding; 20-fold decreased affinity for D-serine; 300-fold decreased affinity for D-alanine; 3-fold decreased affinity for D-proline. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs368093324 [ dbSNP | Ensembl ]

Sequence information

Variant position: 38 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 347 The length of the canonical sequence.
Location on the sequence: CIHERYHSVLQPLDIKVYAD R FTPLTTTDVAAGLWQPYLSD The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Sequence annotation in neighborhood: The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

• Type: the type of sequence feature.
• Positions: endpoints of the sequence feature.
• Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 347	D-amino-acid oxidase
Binding site	37 – 37
Binding site	38 – 38
Binding site	43 – 43
Binding site	44 – 44
Binding site	45 – 45
Binding site	49 – 49
Binding site	50 – 50
Binding site	51 – 51
Binding site	53 – 53
Mutagenesis	31 – 31	D -> H. Increases affinity for the FAD cofactor and D-serine. Decreases the cellular ratio of D-serine to L-serine.

Literature citations

Structural and mechanistic insights into ALS patient derived mutations in D-amino acid oxidase.
Khan S.; Upadhyay S.; Dave U.; Kumar A.; Gomes J.;
Int. J. Biol. Macromol. 256:128403-128403(2024)
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF VARIANT ALS HIS-38 IN COMPLEX WITH FAD AND INHIBITOR BENZOATE; FUNCTION; CATALYTIC ACTIVITY; COFACTOR; BIOPHYSICOCHEMICAL PROPERTIES; SUBUNIT; CHARACTERIZATION OF VARIANTS ALS HIS-38; TRP-199 AND ARG-201;
Questioning on the role of D amino acid oxidase in familial amyotrophic lateral sclerosis.
Millecamps S.; Da Barroca S.; Cazeneuve C.; Salachas F.; Pradat P.F.; Danel-Brunaud V.; Vandenberghe N.; Lacomblez L.; Le Forestier N.; Bruneteau G.; Camu W.; Brice A.; Meininger V.; LeGuern E.;
Proc. Natl. Acad. Sci. U.S.A. 107:E107-E108(2010)
Cited for: VARIANT ALS HIS-38;